Background: Circulating fatty acids are highly correlated with each other and analyzing fatty acid patterns could better capture their interactions and their relation to prostate cancer. We aimed to assess the associations between data-derived blood fatty acid patterns and prostate cancer risk.

Methods: We conducted a nested case-control study in the Physicians’ Health Study. Fatty acids levels were measured in whole blood samples of 476 cases and their matched controls by age and smoking status. Fatty acid patterns were identified using principal component analysis. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI).

Results: Two patterns explaining 40.9% of total variation in blood fatty acid levels were identified. Pattern 1, which mainly reflects polyunsaturated fatty acid metabolism, was suggestively positively related to prostate cancer risk (ORquintile 5 vs. quintile 1=1.37, 95%CI=0.91–2.05, Ptrend=0.07). Pattern 2, which largely reflects de novo lipogenesis, was significantly associated with higher prostate cancer risk (ORquintile5 vs quintile1=1.63, 95%CI=1.04–2.55, Ptrend=0.02). This association was similar across tumor stage, grade, clinical aggressiveness categories and follow-up time.

Conclusion: The two patterns of fatty acids we identified were consistent with known interactions between fatty acid intake and metabolism. A pattern suggestive of higher activity in the de novo lipogenesis pathway was related to higher risk of prostate cancer.